Various chemotherapies are used for better remission of symptoms of multiple myeloma as it is not a curable disease. This study was carried out to evaluate the response of melphalan plus prednisolone therapy for the treatment of Multiple myeloma. The study was conducted in the outpatient department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January to December 2009. A total of 21 patients were included in this study. Combinations of melphalan plus prednisolone were given. Data were analyzed by paired 't' test to evaluate the response after treatment. Most of the patients were within 40-60 years with a male predominance. Haemoglobin level significantly raised after therapy (p<0.001) and ESR was found significantly reduced of these patients after treatment (p<0.001). On the other hand no significant change seen in calcium level before & after therapy (p=0.713). Significantly raised albumin and B2 microglubulin level were also found after treatment (p<0.001). After therapy with malphalan plus prednisolone, 11(52.38%) patient's M Protein reduction was >75%, 7(33.33%) patients M Protein reduction was 50-75%, 1(9.5%) patient's M Protein reduction was >25-50% and 1(12.50%) patient's M Protein reduction was <25%. Mean±SD M protein values before & after therapy were 50.23±19.49 gm/l and 21.01±16.11 gm/1 respectively. M protein level significantly reduced after treatment (p<0.001).