OBJECTIVES:: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive multifactorial disease with limited successful treatment. Hesperidin possesses potent anti-inflammatory and anti-oxidant property. Hence, the objective of present investigation was to evaluate the effect of hesperidin against bleomycin (BLM) induced pulmonary fibrosis by assessing various behavioral, biochemical, molecular and ultrastructural changes in the laboratory rats. METHODS:: IPF was induced in male Sprague-Dawley rats by single intratracheal BLM (6 IU/kg) injection followed by hesperidin (25, 50 and 100 mg/kg, p.o.) or Methylprednisolone (10 mg/kg, p.o.) treatment for 28 days. Sham control rats received saline instead of BLM. The lung function test, biochemical, histopathological and molecular changes were analyzed in lung and bronchoalveolar lavage fluid (BALF). RESULTS:: Treatment with hesperidin significantly restored (p < 0.05) the BLM-induced alteration in body weight, lung index, lung function test, and hematology. The altered total and differential cell count in BALF and blood was significantly restored (p < 0.05) by hesperidin treatment. The decreased peripheral blood oxygen content after BLM instillation was significantly increased (p < 0.05) by hesperidin treatment. Hesperidin significantly enhanced (p < 0.05) the BALF and lung antioxidant status, through modulating the SOD, GSH, MDA, NO level and Nrf2 mRNA expression. The altered mRNA expression of lung inflammatory markers (TNF-α and IL-1β) were significantly restored (p < 0.05) by hesperidin treatment. BLM-induced histological inflammatory and fibrotic insult in the lung which was reduced by hesperidin treatment. CONCLUSIONS:: Hesperidin has potential anti-fibrotic efficacy through induction of Nrf2 which in turn modulated anti-inflammatory molecules to reduce pathogenesis of BLM-induced pulmonary fibrosis.