The purpose of the study was to probe the therapeutic effect of baicalin on immunosuppression in the mouse model of cecal ligation and puncture (CLP)-induced sepsis. Mouse model was established by employing the procedure of CLP. The proliferation of T lymphocytes was measured using CFDA-SE staining and MTT method, and the proliferation index was determined to assess the proliferation status of the outer peripheral and mesenteric cells of the lymph node in various treatment groups. Griess reagent was used to detect serum NO concentrations. The CLP mice treated with baicalin showed reduced mortality and improved physical appearance as compared to the untreated animals. The locomotion and coat color of the baicalin-treated mice were normal compared to those of untreated CLP mice. Additionally, upon dissecting, only little abscess and adhesions were observed in their peritoneal cavity. The atrophy of thymus gland and spleen in the septic mice was significantly ameliorated in baicalin-treated CLP mice. Baicalin also suppressed the serum NO levels and promoted the proliferation of peripheral lymphocytes in CLP mice. Baicalin reduced the mortality in septic mice, exhibiting a thymus gland and spleen protecting effect. The results suggest that baicalin mediated its protective effect against CLP-induced sepsis by inhibiting T lymphocytes apoptosis and serum NO concentrations.