The purpose of the current study was to investigate the protective effect of niacin on acute lung injury (ALI) by the downregulation of the nuclear factor (NF) -κB pathway in rats with hemorrhagic shock (HS). HS was induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean arterial pressure of 20-25 mmHg for 30 min. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose of niacin (360 mg/kg, HS + LD-NA), or a high dose of niacin (1080 mg/kg, HS + HD-NA) were administered through an orogastric tube. The survival of the subjects was observed for 72 hours, and a separate set of animals was killed at 6 hours post-HS induction. We measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced and oxidized glutathione (GSH and GSSG), and malondialdehyde (MDA) levels and histological damage in the lung tissue. We also measured tumor necrosis factor (TNF) -α and interleukin (IL) -6 levels in the lung tissues. The survival rates at 72 hours post-HS induction of the sham, HS, HS + LD-NA, and HS + HD-NA groups were 6/6 (100%), 0/9 (0%), 1/9 (11.1%), and 3/9 (33.3%), respectively. A high dose of niacin increased the lung NADPH level and the GSH/GSSG ratio, decreased the lung MDA level, downregulated the NF-κB pathway, suppressed TNF-α and IL-6 mRNA expressions in the lung tissue, and attenuated histological lung damage. A high dose of niacin attenuated lung inflammation and histological lung damage, and improved survival after HS in rats. Its therapeutic benefits were associated with the increase in the GSH/GSSG ratio, the decrease in oxidative stresses, and the downregulation of the NF-κB pathway.