Interleukin (IL)-11 is a multifunctional cytokine that stimulates hematopoietic progenitor cells and exerts a series of important immunomodulatory effects. Recombinant human interleukin-11 (rhIL-11) has been shown to increase platelet counts in animals and humans and is the only drug approved for use in chemotherapy-induced thrombocytopenia (CIT). rhIL-11 is 19 kDa protein (1) that lacks the N-terminal proline in compare with wild type and has been produced in recombinant E. coli. A synthetic gene of human interleukin 11 was designed, codon optimized, cloned and expressed in E.coli BL21 (DE3) and E. coli Rosetta (DE3) using a pET-15b expression vector. In this study we compared two strategies for better expression of heterologus protein by using two different E. coli systems. As the results show, expression of codon optimized 6His-interleukin 11 in E. coli Rosetta (DE3) was better in comparison with E. coli BL21 (DE3). Not only codon optimization, but appropriate strain selection has a great effect on recombinant protein production in E. coli.