Background and Objective: Human T-Cell Lymphotropic Virus Type I (HTLV-I) is endemic in northeast of Iran. Although chronic inflammation of spinal cord seems to play a major role in the disease pathogenesis, immunomodulatory treatments have not shown significant improvement in disease symptoms. This study was conducted to evaluate the effect of sodium valproate in combination with Peg-Interferon (Peg-IFN) and prednizolone on proviral load and inflammatory factors of patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Materials and Methods: In this pilot clinical trial, 10 HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) patients, referred to HTLV- 1 clinic of Qaem Hospital of Mashhad, Iran in 2012, were treated with sodium valproate, Peg-IFN and prednizolone for 6 months. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll Hypaque and the RNA was extracted from PBMCs. Complementary DNA was synthesized using TaqMan Gold RTPCR Kit. A real-time PCR TaqMan method was designed and optimized for evaluation of Rel-A, Creb and IL-1 genes expression. Results: The analysis in this study indicated that proviral load and IL-1 mRNA expression in patients were significantly lower after treatment. Despite this decline, Creb and IL-1 mRNA expression was not significant. Conclusion: The combination of sodium valproate, Peg-IFN and prednizolone seems an effective treatment for proviral load and relatively efficient for damaging inflammatory factors of HAM/TSP; however, further studies with sufficient sample sizes are necessary.