Objective To evaluate the renal toxicity of vancomycin hydrochloride and irbesartan tablets using the zebrafish model. Methods After construction of AB zebrafish kidney model, the fish were treated with drug after fertilization 2 days (2 dpf) to 5 dpf. At the end of the experiment, the number of renal edema zebrafish was counted in each experimental group to evaluate the renal toxicity of drugs. Results The zebrafish development was normal and no obvious toxicity at the dose of 16?4 ng/fish (1/10 MNLD) for vancomycin, and zebrafish renal edema occurred rate was 3?3%, 10% and 10% respectively at the dose of 54?7 ng/fish (1/3 MNLD), 164 ng/fish (MNLD) and 273 ng/fish ( LD10 ) with the death rate of 0%, 0% and 16?7%, respectively, which indicated that there was significant renal toxicity of vancomycin at the dose of 54?7 ng/fish (1/3MNLD) to 273 ng/fish (LD10). Irbesartan didn’t induce renal toxicity at the dose of 8?3 μg/mL (1/10 MNLC) to 91 μg/mL (LC10). Conclusions The zebrafish model of renal toxicity can be used for the early evaluation of drug renal toxicity and we made evaluation of the renal toxicity of vancomycin and irbesartan with this model.