Abstract: Objective To establish a model of renal ischemia-reperfusion injury (IRI) in rats and study the effect and mechanism of osthole on renal IRI in rats.Methods A rat model of renal IRI was constructed by clamping the left renal pedicle of the rats for 45 min, removing the right kidney, and restoring the renal blood flow for 24 h. Fifty SD rats were randomly divided into sham operated group, renal IRI group, and osthole (low, middle, high) dose groups. 45 min before operation, osthole (5, 10, and 20 mg/kg) was given by intraperitoneal injection in osthole groups. In the sham operated group and renal IRI group, the same volume of normal saline was intraperitoneally injected 45 min before operation. RT-PCR was used to detect the mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). ELISA was used to detect serum creatinine (SCr), blood urea nitrogen (BUN), MCP-1, TNF-α and IL-6. Hematoxylin eosin staining (HE) was used to examine the pathological morphology of renal tissues. The thiobarbituric acid colorimetric method was used to measure malondialdehyde (MDA) content in renal tissues. The xanthine oxidase method was used to determine the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx).Results As compared with sham operated group, renal pathological changes were aggravated, SCr, BUN, MCP-1, TNF-α, IL-6 and MDA levels were significantly increased, and SOD, CAT and GPx activity decreased significantly in IRI group. As compared with IRI group, the pathological changes of renal tissues were significantly alleviated, SCr, BUN, MCP-1, TNF-α, IL-6 and MDA were significantly decreased in a concentration-dependent manner, and SOD, CAT and GPx activity increased in a dose-dependent manner in osthole-treated groups.Conclusions Osthole has protective effects on renal IRI in rats, which may be related to the inhibition of inflammation and oxidative stress.