We have reported the neuroprotective effect of cysteinyl leukotriene receptor 1 (CysLT1) antagonists on cerebral ischemia. Here, we further determined the protective effect of pranlukast, a CysLT1 receptor antagonist, on brain cold injury in mice. Brains were injured by placing a cooled metal probe on the skull surface for 30 s. We found that pranlukast significantly reduced cold-induced lesion volume (0.3 mg/kg) and the percentage increase in lesioned hemisphere volume (0.03-0.3 mg/kg) 24 h after injury, but did not show any effect 72 h after injury. Pranlukast also significantly inhibited neuron loss 24 h (0.1 mg/kg) and 72 h (0.1-0.3 mg/kg) after injury, and decreased the density of degenerated neurons 24 h (0.01-0.3 mg/kg) and 72 h (0.03-0.3 mg/kg) after injury. In addition, pranlukast (0.1-0.3 mg/kg) significantly reduced endogenous IgG exudation both 24 h and 72 h after injury. Thus, this study indicates the protective effect of pranlukast on brain cold injury.