Dehydroepiandrosterone sulfate (DHA-S) is one of the successful drugs used to induce cervical ripening. There is growing evidence that interleukin-8 (IL-8) plays an essential role during cervical ripening. IL-8 was found to be hormonally controlled in the cervix. The aim of this research was to study the effect of DHA-S on the function of IL-8 on the cervix. Sixteen pregnant white New Zealand rabbits where tested either by placebo (adeps solidus, n = 4), DHA-S (10 mg, n = 4), IL-8 (100 ng, n = 4) or combination of DHA-S and IL-8 (n = 4). Collagen contents in the cervices were assessed histologically after staining with picrosirius red. The number of neutrophils in 5 random fields of the cervical tissue was counted in all groups. Collagenase, elastase and gelatinase were measured in those groups. The collagen content of the cervices was significantly decreased after treatment with DHA-S, IL-8 or a combination of both drugs compared to the control group (p < 0.004, 0.001 and 0.001, respectively). A maximal decrease in collagen content was found in the DHA-S + IL-8-treated group (71.5%). Neutrophil infiltration was significantly increased in the IL-8 and DHA-S + IL-8-treated groups (p < 0.0001). Neutrophil numbers in the DHA-S + IL-8-treated group were significantly higher than in the IL-8 group (p < 0.006). Collagenase activity was increased in the DHA-S, IL-8 and DHA-S + IL-8 groups compared to the control group (p < 0.02, 0.008 and 0.001, respectively). Elastase activity was also significantly increased in the same groups (p < 0.002, 0.005 and 0.001, respectively). A similar increment was found in gelatinase activity (p < 0.004, 0.0001 and 0.0001, respectively). DHA-S has a synergistic effect with IL-8 during cervical ripening.