Background: Chronic myeloid leukemia (CML) is a clonal myeloid proliferative disorder of primitive haemopoietic progenitor cells. The incidence of CML ranges between 10 and 15 cases/106 /year without any major geographic or ethnic differences. Imatinib mesylate provides good results in the treatment of CML. Early studies demonstrated that Imatinib mesylate can produce clear hematologic and cytogenetic response when used as a treatment of CML patients with positive BCR-ABL gene. Nevertheless, some patient with different stages of CML (chronic, accelerated, or acute phases) either relapse or stay unchanged for a long time after initial doses of treatment. This phenomenon led to the fact that we must explore the possible changes expected to appear if we make some changes in the treatment strategy. Objectives: The present study aimed to evaluate hematologic and molecular responses of CML patients to Imatinib mesylate treatment. Methods: Eighteen CML patients in chronic phase aged (24–65 years) males and females were treated with Imatinib mesylate (400, 500 or 600 mg/day) for sixteen months. Hematologic and cytogenetic changes were analyzed periodically. Results: Overall 18 cases, hematologic response of 14 cases was complete white blood cells (WBCs) decrease to normal range within 4 months) with P value of less than 0.0001 whereas in 4 cases WBCs were decreased slowly (after 8 months). A major cytogenetic response was noticed in 4 cases while in others the response was partially or in minor range. The major hematologic and cytogenetic response was noticed when using 600mg/day of Imatinib mesylate. The correlation appeared as a significant positive correlation between the treatment doses and Hb, hematocrit, MCV, MCH, esinophils%, and monocytes %. And a significant negative correlation between the treatment doses and RDW %, platelets count, WBCs count, and basophils %. On the other hand, no correlation between the treatment doses and RBCs Count, MCHC, Neutrophil % and BCR/APL ratio % Conclusion: It can be concluded that treatment of CML patients with Imatinib mesylate caused complete WBCs decrease to normal range. The major hematologic and cytogenetic response was noticed when using a higher dose of Imatinib mesylate.