Abstract: Objective To investigate histamine-induced changes of the intracortical vessels in the cortical slice of rat brain. Methods Immunohistochemistry was employed to detect the expression of H1 and H2 receptors in the intracortical blood vessels of rats. Histamine-induced constriction of the intracortical blood vessels of the brain slices was observed with differential interference contrast microscope. Measurements of the luminal diameter were made on-line during the course of the experiment and confirmed off-line from the stored images. In order to observe whether histamine H1 and H2 receptors affected histamine-induced constriction, the intracortical blood vessels in the brain slices were pre-treated with H1 receptor antagonist diphenhydramine and H2 receptor antagonist cimetidine. Results Expression of H1 and H2 receptors was detected in the intracortical blood vessels of the rat brain. Histamine (1-100 μmol/L) induced a concentration-dependent constriction from (1.48±0.67)% to (32.91±7.91)%. The reactions to each histamine concentration were significantly (P<0.01) different from each other, with the exception of the highest histamine concentrations (30 and 100 μmol/L) when maximal constriction due to histamine were observed (P>0.05). With pre-treatment of the slice with 10 μmol/L diphenhydramine, application of histamine did not elicit constriction. Pre-treatment of the slice with 10 μmol/L cimetidine did not completely inhibit but somehow significantly weakened vascular constriction in response to histamine treatment at 10 and 30 μmol/L (P<0.05). Conclusion Histamine can induce constriction of the intracortical blood vessels, which is mediated by H1 receptor.