Abstract: [Objective] To investigate the effect of penicillic acid on kidney damage. [Methods] 60 Kunming mice (25–30 days old) were divided into 4 groups randomly, as control, low-dose group, middle-dose group and high-dose group, and penicillic acid was administered per os for 30 days. Renal function，changes of renal pathomorphology，MDA and SOD content of kidney were detected, and the apoptosis of nephridial tissue were detected with terminal deoxynucl neotidyl transferase mediated dUTP nick end labelling (TUNEL) , the gene expression of P53，Bax、Bcl-2、Fas、 Fasl were detected with reverse transcription-polymerase chain raction (RT-PCR).[Results] The effect on kidney damage induced by penicillic acid depends on the dose applied. In comparison with the control group, penicillin acid could significantly enhance the content of BUN, UA, NAG, and MDA, gene expression of P53 and Bax, but significantly decrease the weight of mice, the content of SOD, gene expression of Bcl-2 and gene expression of FAS in female mice. Epithelia of renal tubule were damaged by Penicillic acid with the method of pathological section, such as: vacuolar degeneration, karyopyknosis and karyolysis, which showed that penicillic acid could markedly induce apoptosis in epithelia of renal tubule. [Conclusion] ① Penicillic acid can degrade the weight of mice.②. Epithelia of renal tubule were severely damaged by Penicillic acid with the method of pathological section. ③The main mechanism of kidney damage caused by penicillic acid was lipid peroxidation which could significantly enhance the content of MDA with corresponding decreases in the content of SOD, and the effect depends on the dose applied. ④ Penicillic acid could markedly induce apoptosis in epithelia of renal tubule via promote gene expression of P53 and Bax and inhibit gene expression of Bcl-2. ⑤Toxicity of penicillic acid for male mice was higher than the female.