Aim: Sinusoidal obstructive syndrome (SOS) that develops due to oxaliplatin-based chemotherapy influences morbidity and mortality following surgical treatment of colorectal liver metastases. The aim of this study was to evaluate the protective effect of sildenafil on liver damage (sinusoidal obstructive syndrome (SOS)) that develops due to oxaliplatin-based chemotherapy.Methods: An experimental animal study was conducted and a total of 42 rats were randomly separated into 4 groups as Sham, intraperitoneal chemotherapy (ipCT), ipCT+low-dose sildenafil treatment, and ipCT +high-dose sildenafil treatment. The ipCT was applied once a week for 5 weeks. Histochemical analysis was made in the livers removed from rats.Results: Parenchymal, stromal, and vascular changes were examined, and no statistically significant difference was determined between the groups with respect to the severity of sinusoidal dilatation (P=0.243). The groups significantly differed with regards to centrilobular, peliotic changes and hepatocellular changes (P<0.001).Conclusion: Sildenafil has a protective effect against liver damage that develops due to oxaliplatin-based chemotherapy and prevents the development of SOS during chemotherapy in colorectal cancer patients. Therefore, it could be considered as a treatment strategy.