Objective:To analyze the healing effect of paeoniflorin on the wound of rats and regulation of NGF/Akt/GSK3β pathway on rats with diabetic foot.Methods:60 rats were randomly divided into normal control group, model group, low, medium and high dose paeoniflorin groups, 12 rats in each group. Diabetic foot model was established by intraperitoneal injection of streptozotocin (STZ) and electrothermal scald. Paeoniflorin groups were injected intraperitoneally with 20 mg/kg, 40 mg/kg and 80 mg/kg paeoniflorin, once a day for 21 days. The wound healing rate of the rats was measured. The fasting blood glucose was measured by blood glucose meter, HbAlc, TC, LDL-C and TG were measured by automatic biochemical analyzer. Serum CRP, IL-6, IL-1β and TNF-α were measured by ELISA. The histopathological changes of the wound were examined by HE staining, the levels of NGF, Akt and GSK3 β mRNA in skin tissue were measured by real-time quantitative polymerase chain reaction (RTq-PCR), the protein and phosphorylation levels of NGF, Akt and GSK3 β were determined by Western blot.Results:Compared with the model group, the healing rate the rats' wounded surface in the low, medium and high dose groups of paeoniflorin was increased ( P<0.05). The levels of fasting blood glucose, HbAlc, TC, LDL-C, TG levels and serum CRP, IL-6, IL-1β, TNF-α was decreased ( P<0.05). The expression of rat skin tissue NGF mRNA (0.83±0.12, 3.17±0.11, 4.54±0.25 vs. 0.31±0.06), Akt mRNA (1.71±0.14, 2.96±0.27, 4.10±0.34 vs. 0.97±0.20) increased ( P<0.05), expression of GSK3β mRNA (4.28±0.35, 2.82±0.14, 1.22±0.33 vs. 7.62±0.43) decreased ( P<0.05), expression of NGF (0.46±0.02, 0.70±0.04, 0.87±0.04 vs. 0.30±0.06), Akt (0.51±0.09, 0.63±0.03, 0.79±0.06 vs.0.41±0.05),p-NGF/NGF (0.47±0.06, 0.61±0.04, 0.83±0.07 vs. 0.25±0.03), p-Akt/Akt(0.54±0.08, 0.83±0.11,0.96±0.07 vs. 0.13±0.05) was increased( P<0.05), the expression of GSK3β (0.67±0.05, 0.54±0.04,0.45±0.03 vs. 0.86±0.05), and the ratio of p-GSK3β/GSK3β (0.78±0.09, 0.64±0.07, 0.42±0.07 vs. 0.97±0.05) was decreased ( P<0.05), and the changes of each index were dependent on the dose of paeoniflorin. Conclusion:Paeoniflorin can regulate the level of blood glucose and blood lipid, inhibit the level of serum inflammatory factors and promote the healing of the wound in diabetic foot rats, and its mechanism may be related to the regulation of NGF/Akt/GSK3β pathway.