Sjögren's disease (SjD), a systemic autoimmune disease, suffers from restricted treatment choices. The activation of salivary gland epithelial cells and abnormal auto-reactive B cells, triggering cytokine and autoantibody generation, is key to its immunopathogenesis. Carboxyamidotriazole (CAI) was reported to have anti-inflammatory properties by reducing cytokines, yet its role in SjD was unknown. In this research, we targeted to probe CAI's potential treatment effect on SjD-like NOD/Ltj mice and its mechanism. Utilizing the salivary glands of these mice, we employed HE staining, ELISA, immunohistochemistry and flow cytometry. Findings revealed that CAI augmented salivary secretion, decreased water intake and serum autoantibody levels, suppressed histological alterations and lymphocyte foci, and diminished inflammatory factors such as IL-1β and IL-6. It also blocked IκBα degradation and p65 nuclear translocation.