Abstract: The association between vitamin D deficiency and asthma epidemic has been recognized. Tumor necrosis factor (TNF)-α and chemokines play important roles in pathogenesis of asthma. However, whether vitamin D has immunoregulatory function on TNF-α and chemokines expression in human monocytes is still unknown. The human monocytic cell line, THP-1 cells and human primary monocytes were pretreated with various concentration of 1α,25-(OH)2D3 for 2 h before stimulation with lipopolysaccharide (LPS). Supernatants were collected 24 or 48 h after LPS stimulation. The levels of TNF-α, interferon-inducible protein 10 (IP-10)/CXCL10 (the Th1-related chemokine), macrophage-derived chemokine (MDC)/ CCL22 (the Th2-related chemokine), and interleukin 8 (IL-8)/CXCL8 (the neutrophil chemoattractant) were measured by ELISA. 1α,25-(OH)2D3 could significantly suppress TNF-α and IP-10 expression in LPS-stimulated THP-1 and human primary monocytes. However, 1α,25-(OH)2D3, especially in higher concentration, could significantly enhance MDC expression. 1α,25-(OH)2D3 had no significant effects on IL-8 expression. We found 1α,25-(OH)2D3 could significantly suppress TNF-α and Th1-related chemokine IP-10, which both play important roles in pathogenesis of severe refractory asthma and autoimmune diseases. However, 1α,25-(OH)2D3 enhanced Th2-related chemokine MDC, which may result in Th2 inflammatory cell recruitment and thus adversely affect asthmatic patients. Although vitamin D has potential utility in the treatment of asthma and autoimmune diseases, excessive use of vitamin D may not be suitable in patients with Th2 allergic diseases.