The present study was designed to evaluate the protective effects of Juglans regia kernel extract against cigarette smoke extract (CSE)-induced lung toxicities in Wistar rats. Prophylactic treatment of methanolic extract of J. regia kernel at the doses of 50 mg/kg b.wt. and 100 mg/kg b.wt was given by gavage to Wistar rats for 1 week prior to CSE exposure. Female Wistar rats were administered with single dose (1.3 mL/kg b.wt.) of CSE through intratracheal instillation. Lung injury markers lactate dehydrogenase (LDH) activity, total cell count, total protein and reduced glutathione (GSH) in bronchoalveolar lavage fluid (BALF) were evaluated. Glutathione reductase (GR), xanthine oxidase (XO) and catalase activities were measured in lung tissue. J. regia extract significantly decreased the levels of LDH, total cell count, total protein and increased the GSH level in BALF, it also significantly restored the levels of GR, catalase and reduced the XO activity in lung tissue. Total polyphenolic content of J. regia kernel extract was found to be 96 ± 0.81 mg gallic acid equivalent (GAE)/g dry weight of extract. In DPPH (2,2-Diphenyl-1-Picrylhydrazyl) assay, the extract shows high free radical scavenging potential. On the basis of these results, protective role of J. regia extract against CSE-induced acute lung toxicity in Wistar rats is suggested.