Objective: To investigate the effect of local hIL-10 gene therapy on experimental periodontitis in rats and to elucidate the mechanism underlying this effect. Material and methods: Experimental periodontitis was induced in ovariectomized (OVX) rats using a silk ligature. We then injected 5g of hIL-10 plasmid with 5l of liposomes or 5g of vector plasmid with 5l of liposomes into the palatal side of the gingival mucosa of the upper left second molar once every two days. The rats were killed 48hours after the seventh injection. The body weight; bone mineral density of the whole body, pelvis and spine; resorption of the alveolar bone; and number of cytokine-positive cells were measured to determine the effects of hIL-10 on the periodontal tissue. Results: hIL-10 was expressed in periodontal tissues after local gene delivery. The expressed hIL-10 protein inhibited alveolar bone resorption and downregulated IL-1, IL-6, TNF-, RANKL and MMP-8 in the periodontal ligament in the root furcation region. Conclusions: Local hIL-10 gene transfer suppressed alveolar bone resorption in OVX rats, and this effect was probably associated with the decline in the expression of pro-inflammatory cytokines in the periodontal tissues.