Progesterone plays an important role in maintaining pregnancy. The success of pregnancy depends on the balance of immune response between the mother and the fetus. Progesterone regulates the immunological response through progesteroneinduced blocking factor (PIBF) which is synthesized by lymphocytes. Progesterone-induced blocking factor inhibits the production of arachidonic acid, reduced NK cell activity, and modulates the cytokine balance by increasing interleukin-10 (IL-10) level that is produced by Th2. This study aims to determine the roles of natural progesterone administration on PIBF and IL-10 levels and the increase in gestational length. This is an experimental research with pre-and post-test design. Subjects were pregnant women who met the criteria (n = 22). The treatment was done for 7 days. Progesteroneinduced blocking factor and IL-10 levels were measured before and after the administration of natural progesterone and the length of gestation were noted. The study was conducted at Dr Hasan Sadikin Hospital within July to December 2013.Results showed that after the administration of natural progesterone, there were increases on PIBF (p = 0.039) and IL-10 levels (p = 0.031). A positive correlation was noted between PIBF and IL-10 levels (r = 0.549; Spearman rank correlation test). There was also positive correlation between PIBF serum level (moderate strength correlation) and the length of gestation (r = 0.428; Point biserial correlation test). Progesterone-induced blocking factor serum level had more influence on the prolongation of the pregnancy compared to IL-10 level (OR: 1.016, 95% CI: 1.001 to 1.03; p = 0.033).Increased levels of PIBF and IL-10 after the administration of natural progesterone on the impending preterm delivery may prolong the gestation. Progesterone-induced blocking factor serum level have more dominant role in prolongation of gestation compared to IL-10.