Objective:To evaluate the clinical efficacy of Gushen Jianpi Huashi Decoction combined with irbesartan in the treatment of spleen and kidney deficiency syndrome of diabetic nephropathy (DN).Methods:According to random number table method, 97 patients with DN who met the inclusion criteria and from January 2018 to September 2020 were randomly divided into two groups, 48 in the control group and 49 in the study group. The control group took irbesartan on the basis of routine treatment of western medicine, and the study group took Gushen Jianpi Huashi Decoction on the basis of the control group. Both groups were treated for 14 days as a course of treatment, a total of 6 courses of treatment. Traditional Chinese Medicine (TCM) syndrome scores were performed before and after treatment, BUN and SCr levels were detected by automatic biochemical instrument, and serum IL-6, TNF-α, and CRP levels were detected by ELISA. The Urinary microalbumin excretion rate (UAER) was measured by radioimmunoassay, and the clinical efficacy was evaluated and adverse reactions were recorded.Results:The total effective rate was 91.8% (45/49) in the study group and 75.0% (36/48) in the control group, and there was significant difference between the two groups ( χ2=4.99, P=0.025). The scores of TCM syndrome in the study group was significantly lower than that of the control group ( t=29.75, P<0.01). After treatment, the serum BUN [(4.49 ± 0.68) mmol/L vs. (5.16 ± 0.61) mmol/L, t=5.11], SCr [(63.42 ± 4.09) μmol/L vs. (69.01 ± 4.35) μmol/L, t=6.52] and UAER [(72.58 ± 5.88) μg/min vs. (85.63 ± 6.49) μg/min, t=10.44] in the study group were significantly lower than those in the control group ( P<0.01), the serum IL-6, CRP and TNF-α levels in the study group were significantly lower than those in the control group ( t values were 9.44, 7.24 and 18.08, respectively, P<0.01). During the treatment, the incidence of adverse reactions was 14.6% (7/48) in the control group and 16.3% (8/49) in the study group, but there was no significant difference between two groups ( χ2=0.06, P=0.812). Conclusion:The Gushen Jianpi Huashi Decoction combined with irbesartan can improve the renal function of DN patients, reduce the level of inflammatory cytokines and improve the clinical effect.