Objectives: We aimed to assess the effect of Hippophae rhamnoides extract (HR) on oxidative stress induced by cisplatin (Cis) in rat small intestine tissue by evaluating the biochemical and gene expression levels and histopathological changes. Materials and methods: The control group and Cis group received distilled water, while the HR25+cisplatin (HR25+Cis) group and the HR50+cisplatin (HR50+Cis) group were given HR 25 and 50 mg/kg, respectively, orally for seven days. HR25+Cis, HR50+Cis, Cis groups were injected with a single dose of intraperitoneal cisplatin on the first day. After sacrifice, the jejunum of each rat was removed for the assessment of oxidants and antioxidants. Analyses of the gene expression (for IL-1ß and TNF-α) and histopathological changes evaluated. Results: HR significantly inhibited the increase of oxidants and the decrease of antioxidants caused by cisplatin in the jejunal tissue. IL-1β and TNF-α gene expression levels were almost the same in both the HR50+Cis and the control groups. HR better prevented increase of the serum levels of IL-1β and TNF-α in animals at 50 mg/kg dose compared to 25 mg/kg dose. We confirmed that HR prevented the histopathological changes caused by cisplatin. Conclusions: It was concluded that oxidative stress caused by cisplatin may be preventable by co-administered HR.