Abstract: Objective: To investigate the mechanism of free fatty acids regulating renal injury through IRE1 / XBP1 pathway in hypertriglyceridemic pancreatitis. Methods: 48 male C57BL/6 mice were randomly divided into control group (CON group), severe acute pancreatitis group (SAP group), hypertriglyceridemic pancreatitis group (HTGP group) and CD36 inhibitor group (SSO group). At 24h after corresponding treatment, blood samples, pancreas and kidney tissues were obtained for serological detection, pathological analysis and immunofluorescence staining. Results: Compared with SAP group, HTGP group had higher levels of triglyceride and free fatty acids, and the severity of pancreatitis and renal injury in HTGP group were more severe. In the renal tissues of HTGP group, the expression levels of IRE1 and XBP1 protein related to endoplasmic reticulum stress and CD36 protein which mediated free fatty acid uptake were higher than those in SAP group. Additionally, after administration of CD36 inhibitor in HTGP group, the pancreatic and renal injury, the levels of inflammatory factors and the expression levels of IRE1 and XBP1 in renal tissue decreased significantly in SSO group as compared to HTGP group. Conclusion: In hypertriglyceridemic pancreatitis, CD36 mediated free fatty acids may activate endoplasmic reticulum stress through IRE1 / XBP1 pathway to regulate related renal injury.