Objective · To investigate the effects of estrogen deficiency on Notch signaling pathway in osteoarthritis via an estrogen deficiency-osteoarthritis model. Methods · Twenty female SD rats were randomly assigned to the experimental group (undergoing bilateral ovariectomy) and the control group (sham operation). Each group was further divided into the osteoarthritis subgroup (injection of collagenase into the articular cavity) and the non-osteoarthritis subgroup (injection of normal saline into the articular cavity). Knee specimens were collected after 6 weeks and the morphological changes of the articular cartilage were observed. Expressions of interleukin-1β (IL-1β), matrix metalloproteinases-1 (MMP-1), type Ⅱ collagen (Col Ⅱ), and Notch2 were measured with immunohistochemistry. Results · The degeneration of articular cartilage was more severe in the experimental-osteoarthritis subgroup than in the control-osteoarthritis subgroup. The expressions of IL-1β and MMP-1 in the experimental-osteoarthritis subgroup were higher and the expressions of Col Ⅱ and Notch2 were lower. The differences in measurement results of related indexes between the experimental-non-osteoarthritis subgroup and the control-non-osteoarthritis subgroup were not significant. Conclusion · The estrogen deficiency can down-regulate the expression of Notch signaling in cartilage tissues of rats with osteoarthritis.