Background: In Egypt, carcinoma of the bladder is the foremost oncologic problem. It constitutes 30.3% of all cancers at the National Cancer Institute. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis and are involved in the process of tumor invasion and metastasis in several malignant tumor entities. Aim of the work: Our aim is to study the expression of MMP-2 and TIMP-2 in bladder tissue in patients with bladder cancer and chronic bilharzial cystitis to define there role in these diseases. Patients and Methods: Seventy-five patients were included in the study: 50 cases with malignancy, 15 with chronic bilharzial cystitis and 10 individuals with apparently normal urothelium were taken as controls. Biopsies were taken by TUR or cold-cup biopsy after bladder mapping. Expression and intensity of MMP-2 and TIMP-2 in bladder tissue was determined by immunohistochemical techniques. Results: We found that both MMP-2 & TIMP-2 immunoreactivity were higher in malignancy group compared to other groups (P<0.001) & correlated with increasing tumor grade & stage (P<0.001). MMP-2 was higher in squamous cell carcinoma compared to transitional cell carcinoma (P<0.01) while TIMP-2 is equally expressed. Regarding the impact of bilharziasis on MMP-2 & TIMP-2 expression 40% of bilharzial cystitis cases were MMP-2 immunoreactive while only 20% were TIMP-2 immunoreactive. We also foud that MMP-2 expression was significantly higher in bilharzial associated malignant cases in comparison to non-bilharzial malignant cases (p< 0.001). In contrast to MMP-2 expression, TIMP-2 expression was significantly higher in non-bilharzial associated malignant cases in comparison to bilharzial associated malignant cases (p< 0.01). Conclusion: MMP-2 & TIMP-2 could be useful biomarkers for prediction of bladder cancer progression.