People living with diabetes (DM) are at increased risk to become infected with Mycobacterium tuberculosis, to progress from latent tuberculous infection to active tuberculosis (TB) disease, and to suffer adverse TB treatment outcomes. In some low- and middle-income countries, DM prevalence among newly diagnosed TB patients exceeds 40%. Despite the global significance of DM as an acquired TB risk factor, the biochemical and cellular mechanisms of susceptibility are incompletely understood. This review summarizes the landscape of basic research using animal models of the TB-DM interaction, and the extent to which findings in animal studies reflect or may explain the clinical features of TB-DM comorbidity in humans. We conclude that immunopathy results in damage to major organs as a complication of DM, likely operating through biochemical pathways such as those responsible for diabetic nephropathy, neuropathy, retinopathy, cardiovascular disease, and delayed wound healing. Insights gained from animal models can inform optimal management of TB-DM comorbidity and will be essential for pre-clinical development of therapeutic countermeasures.