INTRODUCTION AND OBJECTIVE: Stress urinary incontinence (SUI) is a major health problem that has many social and economic impacts, so we evaluated the long-term effect of locally and systemically administrated adipose tissue-derived mesenchymal stem cells (ADMSCs) on the treatment of SUI-induced in a rat model. METHODS: Thirty-two female Sprague-Dawley rats were randomly allocated into 4 groups (8 rats each); control, SUI, local ADMSCs and systemic ADMSCs groups. SUI was induced by vaginal dilatation of the rats via inflating the balloon of a urethral catheter with 5 mL sterile saline in the vagina for 8 hours. Rats then received 0.9% saline, local ADMSCs treatment (periurethal injection at 5 and 7 o’clock positions of the vesico-urethral junction) and systemic ADMSCs treatment (injection in the tail vein) in SUI, local and systemic ADMSCs groups, respectively for 4 weeks. Urodynamic study in terms of abdominal leak point pressure (ALPP), threshold pressure (TP) and bladder capacity (BC) was performed. Rats were then sacrificed and their periurethral regions were sent for routine histopathological examination. RESULTS: There was significant improvement in the results of urodynamic study in terms of ALPP, TP and BC after administration of either local or systemic ADMSCs for 4 weeks relative to SUI group (figure 1). There was also significant evidence of regeneration of the muscle layers in the periurethral regions with less inflammation and fibrosis in local and systemic ADMSCs groups compared to SUI group (figure 2). Moreover, the locally administrated ADMSCs significantly provided more favorable effects than the systemically administrated ADMSCs. CONCLUSIONS: Long-term administration of ADMSCs either locally or systemically in the periurethral regions in SUI improves the morphological and urodynamic dysfunctions of the urethral sphincters.