The present study was designed to investigate the influence of Se deficiency on serum histamine concentration and the expression of histamine receptor in the jejunum of chickens. Forty neonatal chickens were randomly divided into two groups. Experimental chickens were fed a low-Se diet (0.034 mg/kg), whereas chickens in the control group were fed a diet with a Se level of 0.229 mg/kg. Ten chickens were sacrificed on days 30, 45, 60 and 75. Blood and jejunum samples were collected. Histamine concentration in the jejunum was measured by ELISA, the jejunal mast cell (MC) ultrastructure was studied by transmission electron microscopy, and the expression level of histamine H2 receptor (H2R) mRNA in the jejunum was examined using real-time PCR. The jejunal histamine concentration in chickens fed the low-Se diet was significantly higher than that in the control group (P < 0.01). Se deficiency induced degranulation of MC in the jejunum of chickens in the low-Se diet group; their cytoplasm was filled with fused granules and vacuoles. The expression level of jejunal H2R mRNA in chickens fed the low-Se diet was also significantly higher than that in the control group (P < 0.01). The results obtained suggest that Se deficiency stimulates MC degranulation and release of histamine, binding H2R promotes both regulation of digestion and cell proliferation while protects the jejunum from injury induced by Se deficiency.