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Problem: A successful human pregnancy requires cytotrophoblasts from the fetal portion of the placenta to adopt tumor-like properties. But unlike tumor metastasis, cytotrophoblast invasion is highly regulated both spatially and temporally. The mechanisms that regulate human trophoblast invasion are understood poorly., Method of Study: With a view to obtain some findings on the mechanisms that regulate human trophoblast invasion, we applied the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) method to compare the expression of invasion-associated genes in cytotrophoblasts isolated from first- and third-trimester placental tissues., Results: In trophoblast cells of first-trimester pregnancy, the mRNA contents of matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (uPA) were higher than that in the third-trimester cytotrophoblasts, while no difference of MMP-2 mRNA expression level was found between trophoblastic cells of different gestational ages. The expression level of plasminogen activator inhibitors-1 mRNA in first-trimester cytotrophoblasts was shown to be much lower than that in trophoblast cells prepared from third-trimester placental tissues. Furthermore, expression of both tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in cytotrophoblasts were significantly up-regulated in third-trimester when compared with the first-trimester of pregnancy. To further investigate the factors that caused the change of invasion-associated genes expression in trophoblast cells, we found that interleukin-10 (IL-10) could decrease the content of MMP-9 mRNA in cytotrophoblasts of first-trimester gestation, and the magnitude of suppression increased with increasing IL-10 concentration., Conclusion: The gradually reduced trophoblast invasion with gestational weeks might be on account of the change of proteolytic enzymes/activator/inhibitor genes expression. IL-10 could be one of the factors participating in the regulation of trophoblast invasion during gestational process.