Background: The levonorgestrel intrauterine system (LNG-IUS) is a widely recognized intrauterine anti-fertility system, which can alleviate symptoms of uterine leiomyoma. This study aims to evaluate leimyoma cell growth inhibition induced by high concentrations of LNG. Study Design: After treatment with LNG, the growth rate of the cultured primary uterine leiomyoma cells was studied with methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis rate was determined by morphological changes and flow cytometry. Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were performed to measure the differential mRNA and protein expression levels. Results: The proliferation rate of uterine leiomyoma cells was suppressed after treatment with LNG at a minimum concentration of 10 mcg/mL. The inhibitive effect was positively correlated with the LNG concentration and with the incubation time. Flow cytometry showed that the apoptosis rate was increased with the LNG concentration. The mRNA levels of IGF-1, Bcl-2 and survivin were down-regulated significantly after treatment with 10 mcg/mL LNG. Western blot analysis confirmed that the expression of Bcl-2 and survivin was decreased significantly, and the p38 phosphorylation level was increased and caspase 3 was activated remarkably 72 h after treatment with 10 and 20 mcg/mL LNG. Conclusions: This study demonstrated that LNG may suppress the proliferation and induce apoptosis of the uterine leiomyoma cells. © 2010 Elsevier B.V. All rights reserved.