AIM: To observe the effect of cannabinoid receptor (CB1R) agonist WIN55-212-2 on the expression of brain-derived neurotrophic factor (BDNF), c-Fos and protein kinase A beta-catalytic subunit (PKAC-β) in cerebrum cortex after intracerebral hemorrhage (ICH) in rats. METHODS: The intracerebral hemorrhage model of rat was made by the injection of collagenase Ⅶ, and WIN55-212-2 was intraperitoneally (ip) injected 30 min later. The rats were killed for sampling the brain tissues as specimens 24 h after ICH. The methods of immunohistochemical analysis and Western blotting were adopted to detect the expression of PKAC-β and BDNF. The mRNA expression of PKAC-β, c-Fos and BDNF was determined by RT-PCR. RESULTS: WIN55-212-2 obviously improved some nervous deficit symptoms and increased the expression of BDNF at mRNA and protein levels with upregulating the mRNA expression of c-Fos and downregulating the expression of PKA at mRNA and protein levels in the ipsilateral cerebral cortex. The proteins of PKAC-β, c-Fos and BDNF were expressed on the membrane or nucleus of the neuron or in the cytoplasm of glial cells, respectively. CONCLUSION: The expression of BDNF is induced not only by upregulation of c-Fos, but also by downregulation of PKA in WIN55-212-2 treated rats.