The present study was conducted to investigate the effects of histamine on the lipid metabolic disorder in mice loaded with restraint stress. When Kun Ming (KM) mice were exposed to restraint stress for 20 h, the histamine level in both plasma and cerebral regions significantly increased (P<0.01). Moreover, when a lipid emulsion (10% Intralipid) was injected intravenously into the mice, the elimination period of plasma triglyceride was prolonged in the restraint group. Plasma triglyceride was 523 +/- 44 mg/dl at 35 min after the Intralipid administration in the restraint stress group, while it was 436 +/- 41 mg/dl in the restrained mice given histamine at a dose of 50 mg/kg. The improved plasma triglyceride metabolism was well explained by the observations of the significantly up-regulated hepatic triglyceride lipase (HTGL) activity and mRNA expression in response to histamine. These results suggested that the effects of stress-induced histamine on lipid metabolic disorder in mice loaded with restraint stress arose from its anti-stress action and promotion of lipase activity.