Background: To explore vitamin D receptor (VDR) and cyclooxygenase-2 (COX-2) expression in uterine leiomyomas and normal myometrium tissues, and further analyze their correlation in the etiopathogenesis of uterine leiomyomas. Methods: We collected uterine leiomyoma tissues and their paired adjacent normal myometrium tissues from 20 cases of uterine leiomyomas and examined the expression of VDR and COX-2 in the tissues by real-time polymerase chain reaction and Western blotting, respectively. We further analyzed the correlation between VDR and COX-2 as well as their expressions with correlation to the size of uterine leiomyomas. Results: The expression of VDR mRNA in 15 of 20 uterine leiomyoma tissues decreased compared with the healthy uterine smooth muscle tissues (P<0.05). The expression of COX-2 mRNA in 13 of 20 uterine leiomyoma tissues was higher than in the healthy uterine smooth muscle tissues (P<0.05). The Western blotting results also showed that VDR expression decreased and COX-2 expression increased in uterine leiomyoma tissues compared with the expression in healthy uterine smooth muscle tissues. There were 11 cases with VDR expression decreased and COX-2 expression increased in uterine leiomyoma tissues. And there was a negative relevance between VDR and COX-2 expression in the 11 cases (r=-0.628, P<0.05 for transcriptional level; r=-0.612, P<0.05 for protein level). However, there was not significant correlation between VDR and COX-2 expression in total specimen (r=-0.209, P>0.05 for transcriptional level; r=-0.165, P>0.05 for protein level). There was not significant correlation between VDR expression and uterine leiomyoma size, as well as between COX-2 expression and uterine leiomyoma size (r=-0.008, P>0.05; r=0.150, P>0.05, respectively). Conclusions: VDR expression decreased and COX-2 expression increased in uterine leiomyomas compared with the healthy uterine smooth muscles. Decreased VDR expression and high COX-2 expression may play a role in the etiopathogenesis of uterine leiomyomas. There may be a negative relevance between VDR and COX-2 in leiomyomas.