Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infection in immunocompromised individuals. Standard treatment with trimethoprim-sulfamethoxazole is limited by frequent side effects, potential drug resistance, and diminishing efficacy in certain patients, highlighting the need for alternative therapeutic strategies. This study evaluates the therapeutic and prophylactic potential of baicalin (Ba), a flavonoid derived from traditional Chinese medicine, in an immunosuppressed rat model of PCP. The therapeutic experiment involved intragastric administration of Ba at doses of 100, 200, or 400 mg/kg/day for 4 weeks in immunosuppressed rats, in comparison with intragastric administration of TMP-SMZ (50–250 mg/kg/day). Ba treatment demonstrated a dose-dependent reduction in Pneumocystis burden, alongside improved general health and lung histopathological scores, as well as elevated CD4 + T-cell counts, comparable to the effects observed with TMP-SMZ. In the prophylactic experiment, Ba (100 mg/kg/day) was administered intragastrically for 7 weeks, followed by 5 weeks of continued immunosuppression without further Ba treatment. Ba-treated rats exhibited significantly higher CD4 + T-cell counts, lower CD8 + T-cell counts, and attenuated inflammatory cytokine profiles. The effects of Ba treatment are associated with anti-inflammatory and antioxidant activities, regulation of protease/anti-protease balance, and inhibition of pulmonary collagen deposition. These findings support Ba’s potential as an alternative treatment regimen for PCP.