Abstract Background Exercise is a well-accepted strategy to improve lipid and inflammatory profile in individuals with type 2 diabetes (T2DM). However, the exercise intensity having the most benefits on lipids and inflammatory markers in patients with T2DM remains unclear. We aimed to analyse the impact of a 1-year combined high-intensity interval training (HIIT) with resistance training (RT), and a moderate continuous training (MCT) with RT on inflammatory and lipid profile in individuals with T2DM. Methods Individuals with T2DM (n = 80, aged 59 years) performed a 1-year randomized controlled trial and were randomized into three groups (control, n = 27; HIIT with RT, n = 25; MCT with RT, n = 28). Exercise sessions were supervised with a frequency of 3 days per week. Inflammatory and lipid profiles were measured at baseline and at 1-year follow-up. Changes in inflammatory and lipid markers were assessed using generalized estimating equations. Results After adjusting for sex, age and baseline moderate-to-vigorous physical activity (MVPA), we observed a time-by-group interaction for Interleukin-6 (IL-6) in both the MCT with RT (β = − 0.70, p = 0.034) and HIIT with RT (β = − 0.62, p = 0.049) groups, whereas, only the HIIT with RT group improved total cholesterol (β = − 0.03, p = 0.045) and LDL-C (β = − 0.03, p = 0.034), when compared to control. No effect was observed for C-reactive protein (CRP), cortisol, tumour necrosis factor-α (TNF-α), soluble form of the haptoglobin-hemoglobin receptor CD163 (sCD163), triglycerides and HDL-C in both groups (p > 0.05). Conclusions Favorable adaptations on IL-6 were observed in both the HIIT and MCT combined with RT groups following a long-term 1-year exercise intervention in individuals with T2DM. However, only the HIIT with RT prevented further derangement of total cholesterol and LDL-C, when compared to the control group. Therefore, in order to encourage exercise participation and improve inflammatory profile, either exercise protocols may be prescribed, however, HIIT with RT may have further benefits on the lipid profile. Trial registration Clinicaltrials.gov ID: NCT03144505