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Introduction: Estrogen deficiency is the main risk factor of articular cartilage degeneration, leading to postmenopausal osteoarthritis. Moreover, there were imperfect estrogen-responsive elements that did exist in the 5’-untranslated region of Notch1 and Jagged1. So, our aim was exploring the relationship between estrogen deficiency and the Notch signaling in postmenopausal osteoarthritis. Methods: These rats were divided into four groups as follows1. bilateral ovariectomy and intra-articular injection of collagenase, 2. bilateral ovariectomy, 3. intra-articular injection of collagenase, 4. intra-articular injection of normal saline. Histological and immunohistochemical staining of joint cartilage were used to evaluate the osteoarthritis model, including the morphological changes of articular cartilage and the relative expression of osteoarthritic biomarkers (IL-1β, MMP-1, and type II collagen). The Notch signaling expression (Notch2) were detected using immunohistochemical staining. In addition, the correlation between the osteoarthritic biomarkers and the Notch2 was also investigated. Results: The expression level of Notch signaling were significantly decreased in the postmenopausal osteoarthritic joint, comparing with other groups. No significant differences were observed in all noncollagenase induced joint, regardless of whether being undergone ovariectomy. The expression of Notch2 was negatively correlated to IL-1β and MMP-1 in osteoarthritisoppositely, it was positively correlated to type II collagen. Conclusion: the results hinted that estrogen deficiency reduced the expression of Notch signaling in osteoarthritic joint. Thus, the Notch signaling could be a potential target for treating postmenopausal osteoarthritis.