Objective: To observe the therapeutic effect of Shenyanzhixue/ nephritis hemostasis Pill on IgA nephropathy model rats, and to explore its mechanism based on X-box binding protein 1 (XBP1)/Cosmc pathway. Methods: The IgAN rat model was set by the combination of "bovine serum albumin (BSA) + subcutaneous injection of carbon tetrachloride (CCl4) + intravenous injection of lipopolysaccharide (LPS)". The rat model was randomly separated to Control-, Model-, Shenyanzhixue pill-, losartan potassium tablet-, or XBP1 inhibitor-group (n=8). The XBP1 inhibitor group was treated continuously for 4 weeks, and the other groups were treated continuously for 6 weeks. the levels of XBP1, Cosmc and Gd-IgA1 were detected. Results: Shenyanzhixue Pills can significantly reduce urinary protein and red blood cells (P<0.01), which is significantly better than that of Kesu subgroup. XBP1 inhibitor enhanced levels of Gd-IgA1 in blood and decreased Cosmc level in blood. The expression of blood Gd-IgA1 was drastically inhibited in the group, while XBP1 and Cosmc were increased. XBP1 inhibitor increased the deposition of IgA and C3; the Shenyanzhixuewan group significantly decreased their deposition, and decreased the deposition. Conclusion: XBP1 inhibitor significantly increased expression  levels of Gd-IgA1 and decreased the expression levels of XBP1 and Cosmc in blood, intestinal tissue and kidney tissue, and increased urinary protein and red blood cells.