Objective To investigate the expressions of Toll-like receptors and NOD-like receptor (TLR/NLRP) in septic rats with acute kidney injury (AKI) and influence of Radix notoginseng. Methods One hundred and fifty male Sprague-Dawley (SD) rats were selected, and they were divided into three groups: sham operation group, model group and Radix notoginseng pretreatment group with 50 rats in each group. Sepsis rats with AKI models were established by cecal ligation puncture (CLP); only was laparotomy performed in the sham operation group without ligation. The rats in Radix notoginseng pretreatment group were given Radix notoginseng (3 g/kg) for consecutive 3 days by gastric perfusion before treatment, and the sham operation group and sepsis model group rats were given equal amount of normal saline by gastric perfusion. After their blood was collected, at each following time points 6, 12 and 24 hours after modeling, 10 rats in each group were sacrificed, and the kidney specimens were collected. The endotoxin levels were detected by limulus assay; the levels of serum creatinine (SCr) and urea nitrogen (BUN) were detected by automatic biochemical analyzer; serum levels of interleukins (IL-1β, IL-18, IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA); the expression levels of NLRP1/3 and TLR2/4 mRNA and protein in renal tissue were detected by real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western Blot, respectively; the pathological changes of renal tissues were observed by optical microscope. The 4-day and 7-day survival rates were observed in the remaining 20 rats in each group. Results The levels of endotoxin, SCr, BUN, IL-1β, IL-6, IL-18, and TNF-α and the expressions of NLRP1/3, TLR2/4 mRNA and proteins in sepsis model group and Radix notoginseng pretreatment group were significantly higher than those in sham operation group, and the levels of endotoxin, IL-18, and the expressions of NLRP1/3, TLR2/4 mRNA and proteins showed statistically significant differences at 6-hour after operation [endotoxin (kU/L): 61.3±25.7, 56.9±18.6 vs. 0.2±0.1, IL-18 (ng/L): 16.7±5.0, 13.8±2.9 vs. 10.6±2.8, NLRP3 mRNA (2-ΔΔCt): 6.3±1.9, 4.0±1.2 vs. 1.1±0.4, TLR mRNA (2-ΔΔCt): 5.7±1.3, 2.0±0.8 vs. 0.9±0.3, TLR4 mRNA (2-ΔΔCt): 4.4±1.2, 2.3±0.7 vs. 0.6±0.2, NLRP3/β-actin: 38.2±9.3, 26.1±7.2 vs. 18.3±5.1, TLR4/β-actin: 21.9±6.1, 16.2±4.4 vs. 10.9±2.8, TLR4/β-actin: 18.3±6.7, 12.0±3.9 vs. 7.5±2.0, all P < 0.05], the levels of SCr, BUN, IL-1β, TNF-α and IL-6 showed statistically significant differences at 12-hour after operation [SCr (μmol/L): 62.3±21.6, 38.1±13.9 vs. 36.0±11.9, BUN (mmol/L): 16.5±7.2, 6.9±2.6 vs. 6.8±2.5, IL-1β (ng/L): 37.6±10.9, 31.2±9.3 vs. 20.3±6.5, TNF-α (ng/L): 15.6±3.9, 10.2±2.8 vs. 7.3±2.1, IL-6 (ng/L):9.3±2.5, 6.8±1.7 vs. 5.0±1.3, all P < 0.05], the levels of expressions of NLRP3 mRNA and protein were obviously lower than those in sham operation group, and there were statistical significant differences immediately after 6-hour after operation [NLRP1 mRNA (2-ΔΔCt): 0.5±0.1, 0.8±0.2 vs. 1.6±0.5, NLRP3/β-actin: 8.0±2.1, 16.8±5.0 vs. 35.6±10.5, all P < 0.05], and the amplitude changes of the above indexes in Radix notoginseng pretreatment group were obviously smaller than those in sepsis model group (all P < 0.05); the survival rates of 4-day and 7-day in sepsis model group were significantly lower than those in sham operation group [4-day: 25% (5/20) vs. 95% (19/20), 7-day: 15% (3/20) vs. 95% (19/20), both P < 0.05], while the survival rate in Radix notoginseng pretreatment group was significantly higher than that in sepsis model group [respectively 65% (13/20) vs. 25% (5/20), 60% (12/20) vs. 15% (3/20), both P < 0.05]. Conclusions TLR2/4 and NLRP1/3 may be involved in the pathogenesis of AKI of septic rats. Traditional Chinese medicine Radix notoginseng possibly via regulating the expressions of TLR2/4 and NLRP1/3 can reduce the inflammatory response, in turn ameliorate kidney injury in septic rats and improve their renal functions.