Objective: Structural studies of the TIR domains of Toll-like receptors are of great interest, but their production in bacterial cells is a challenging task. Here we investigated the effect of C-terminal disordered regions on the synthesis of TIR domains in the soluble form. Methods: The expression constructs corresponding to the TIR domains of TLR4 and TLR10 with and without C-terminal regions were prepared. The proteins were produced in E. coli cells at different temperatures, inducer concentrations, and cultivation time. The protein yields were quantified by SDS-PAGE imaging and analysis. Results and Discussion: We compared the yields of the soluble TIR domains of TLR4 and TLR10 with and without C-terminal regions, produced in E. coli cells, and showed that in the case of full-length constructs, the protein accumulates exclusively as inclusion bodies, while in the case of truncated ones certain portion of the protein is produced in the soluble form. This finding makes possible production of milligram quantities of soluble recombinant TIR domains in bacteria. Conclusions: The results of the present work contribute to the previously proposed protocols for the production of TLR family TIR domains in the soluble form for structural studies.