Objective: Bladder cancer is a common disease worldwide. The gold standard for diagnosing bladder cancer is cystoscopy and urine cytology. In recent years, researchers try to find molecular biomarkers which alteration in their expression is related to bladder cancer. A new class of markers is microRNAs that are 20-25 nt-long single stranded non-coding RNA molecules, processed from hairpin precursors of 70 nt (pre-miRNA), believed to play important roles in gene regulation. MiR-21 is a cellular microRNA which upregulates in most cancers such as breast, glioblastoma, and prostate. TGF-b is an important gene, involved in a series of cellular processes such as growth, apoptosis and maintenance of homeostasis. TGF-b alteration in bladder cancer has been already reported. TGF-b is also involved in miR-21 maturation, and hence can enhance cellular malignant behavior via production of mature miR-21. Here, we have evaluated the expression and a potential correlation between their expression level and the state of tumorogenesis.Materials and Methods: Bladder tissue was homogenized and total RNA extracted with Trizol reagent. Then to quantify miR-21 expression, considering its short sequence, we used LNA specific primers and real-time PCR technique. Furthermore, for TGF-b detection we used real-time primers coupled with SYBR Green detection. After determining the expression level of miR-21 and TGF-b in tumor and marginal tissue samples of bladder, the obtained data was analyzed by REST 2008 software.Result: Our preliminary data revealed an altersed expression for miR-21 and TGF-b variants in tumor vs. normal tissue samples of bladder. Downregulation of TGF-b variants and overexpression of mir-21 was evident in some cases. Conclusion: Measuring miR-21 expression level with or without TGF-b treatment in bladder cancer cell lines could shed more light on deciphering the MECHANISM of action of TGF-b and miR-21. Also, finding a significant correlation between the expression level of TGF-b and miR-21 has a clinical significant.