Objective The aim of present study was to investigate the protective effect of vitamin U on renal toxicity induced by sodium valproate (VPA) and provide laboratory data for clinical application of VPA. Methods In this study, 48 female rats were used. These animals were randomly divided into 4 groups: control group (group A), vitamin U group (group B), VPA group (group C), vitamin U+ VPA group (group D). Group A was given the same amount of normal saline, group B was given Vit U 50 mg/(kg·d), group C was given VPA 300 mg/(kg·d) and group D was given Vit U 50 mg/(kg·d) firstly, then VPA 300 mg/(kg·d) after 1 hours by gavage. After 2 or 4 weeks of continuous administration, the kidneys were collected from these rats after blood collection. Total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), serum creatinine (Cr), urea (BUN) and uric acid (UA) were detected by automatic biochemical analyzer. Result ① Blood lipid. There were significant differences in TC and LDL between the group A and group C (P<0.05), and the level of TC and LDL in group C were significantly higher. ② Serum biochemical indexes of renal function. There was no significant difference in Cr, UA and BUN four groups at 2w (P>0.05). At 4w, compared with the other three groups, the Cr, BUN and UA level of VPA group were significantly higher (P<0.05). But there was no significant difference between the group A and the group D. ③ Pathological morphology of renal tissue. At 2w, there was no obvious abnormality in renal structures among the four groups. At 4w, inflammatory lesions were only seen in VPA group, and mild inflammatory cell infiltration were seen in other three groups. Conclusion VPA can lead to a higher level of blood lipid. The renal toxicity induced by VPA may have a certain relationship with the time of drug exposure, and vitamin U has a protective effect on the renal toxicity induced by VPA.