This study explores the impact of silymarin, a potent natural flavonoid with robust antioxidant properties, on paclitaxel-induced lung injury. Paclitaxel, a widely used chemotherapeutic agent for cancer, is known for its adverse effects on various organs. The research involved four groups: the Control group (6 animals) received oral saline; the SIL group (6 animals) received 200 mg/kg silymarin orally for 10 days; the PAX group (6 animals) received intraperitoneal paclitaxel (2 mg/kg) for 5 days; and the PAX+SIL group (6 animals) received both treatments. All groups were sacrificed on the 10th day. Histopathological analysis revealed pathological changes in the lung tissue of the PAX group. Immunopositivity of Bax, iNOS, Nf-kB, and IL-6 antibodies was higher in the PAX group compared to silymarin-treated groups. Conversely, Bcl-2 and MUC1 immunopositivity was lower in the PAX group but higher in silymarin-treated groups. Silymarin administration decreased IL-6, Caspase-3, P2x7 and NF-kB p65 immunoreactivity, while increased Bcl-2 immunoreactivity. Protein expression levels of IL-6, Caspase-3, P2x7, and NF-κB were higher in the PAX group but decreased in the PAX+SIL group. Bcl-2 protein expression was lower in the PAX group but higher in the PAX+SIL group. Additionally, antioxidant enzyme levels increased, while MDA levels decreased in the PAX+SIL group. In conclusion, the findings indicate that silymarin effectively ameliorated paclitaxel-induced lung damage, highlighting its potential therapeutic role in mitigating chemotherapy-related side effects.