Aim To study the anti-itching and anti-hypersensitivity effects of Doxepin hydrochloride cream. Methods The effects of Doxepin hydrochloride cream on the pruritus of skin in mice due to 4-AP and guineapigs due to histamine phosphate were observed. The inhibitory actions of it on the increase of abdominal cavity capillary permeability in mice due to acetic acid and the angiectasis of skin in rats due to histamine were also observed. Its effects on the delayed-type hypersensitivity (DTH) of mice due to 2, 4-dinitrochlorobenzol (DNCB) and the homologous passive anaphylaxis of skin in rats were used to investigate its anti-hypersensitivity actions. Results The application of Doxepin hydrochloride cream (50, 125, 250 mg?kg -1) on the skin of mice had significant inhibitory actions on the pruritus of skin caused by 4-AP, and the application of Doxepin hydrochloride cream (10, 25, 50 mg?kg -1) on the skin of guinea pigs also had significant inhibitory actions on the pruritus of skin caused by histamine phosphate. The application of Doxepin hydrochloride cream (10,25,50 mg?kg -1 and 50,125,250 mg?kg -1) on skin inhibited the increase of skin capillary permeability in rats caused by histamine phosphate and the increase of abdominal cavity capillary permeability in mice caused by acetic acid. The application of Doxepin hydrochloride cream (50, 125, 250 mg?kg -1 and 10, 25, 50 mg?kg -1) on skin also significantly inhibited the delayed-type hypersensitivity in mice due to 2, 4-dinitrochlorobenzol and the homogeneous cutaneous anaphylaxis in rats. Conclusions Doxepin hydrochloride cream can relieve itching,inhibit the increase of capillary permeability caused by inflammatory substances. It also has significant inhibitory actions on TypeⅠ and Type Ⅳ allergic reactions.