The prevalence of allergic disease is increasing dramatically in the developed world. Studies of allergic diseases have clearly demonstrated that histamine plays an important role in the pathogenesis of the early-phase allergic response. Histamine effects are mediated by H1, H2, H3, and H4 receptors. The presence of the histamine H4 receptors on leukocytes and mast cells suggests that the new histamine receptor H4 plays an important role in the modulation of the immune system. Thus, histamine H4 receptor is an attractive target for anti-allergic therapy. In our present study, we have generated a histamine H4 receptor model using I-TASSER based on human B2-adrenergic G-protein-coupled receptor. Structurally similar compounds of the three known antagonists JNJ777120, thioperamide, and Vuf6002 were retrieved from PubChem, and database was prepared. Virtual screening of those databases was performed, and six compounds with high docking score were identified. Also the binding mode revealed that all the six compounds had interaction with Asp94 of the receptor. Our results serve as a starting point in the development of novel lead compounds in anti-allergic therapy.