Objective:To explore the protective effect of silent mating type information regulation 2 homolog 1(Sirt1) activator SRT1720 on podocyte injury in puromycin aminonucleoside (PAN) induced minimal change nephrotic rats. Methods:One single dose of puromycin aminonucleoside(150 mg/kg) was injected peroidly into male SD rats to induce the minimal change nephrosis. There are three groups:control group,PAN group,and SRT1720 treatment group. Tweenty-four hours urine protein excretion was detected by Bradford method. Podocyte injury was observed by transmission electron microscope(TEM). The expressions of podocyte slit diaphragm nephrin and podocin were determined by real time RT-PCR and Western blot. Results:①Compared with the control group,urine protein excretion in PAN rats began to increase after three days of puromycin aminonucleoside injection(P < 0.01),and reached a peak to 259.73 mg/24 h at the seventh day. After the treatment of SRT1720 for 3 days,urine protein excretion was significantly decreased(P < 0.01),and dropped to 52.47 mg/24 h in the seventh day. ②Serum albumin levels were significantly decreased[(22.14 ± 3.05)g/L] and serum cholesterol levels increased[(7.03 ± 1.64)mmol/L] in PAN rats as compared with the controls SRT1720 treatment significantly increased serum albumin[(35.48 ± 3.96)g/L] and decreased cholesterol[(2.81 ± 0.41) mmol/L]. ③TEM results showed that podocyte foot processes in PAN groups fused and disappeared widely,and the foot processes fusion was markedly alleviated after SRT1720 treatment. ④Compared to the control group,obvious reduction of nephrin and podocin mRNA and protein in PAN rats was detected(P < 0.05),and the expressions of nephrin and podocin in SRT1720 treatment group were significantly raised (P < 0.05),capable restored to 80%~85% of control group. Conclusion:SRT1720 could decrease urine protein excretion,protective against hypoalbuminuria and hypercholesterol,and podocyte injury in PAN rats.