Aim We aimed to explore the link among IL-6, hs-CRP, and grades of DN in both types of diabetes mellitus (DM). Settings and design We carried out a case–control study on participants selected from the outpatient clinic of Internal Medicine Department. Patients and methods We worked on 91 participants, comprising 78 patients and 13 controls. The patient group was further subdivided into two subgroups: subgroup I [39 patients type 1 DM (T1DM)] and subgroup II [39 patients type 2 DM (T2DM)]. Each subgroup was categorized according to the urinary albumin excretion rate into three divisions: A (<20 μg/min), B (20–200 μg/min), and C (>200 μg/min). We applied history taking, clinical examination, routine investigation, and IL-6 with hs-CRP testing to all participants. Statistical analysis We used Shapiro–Wilk test, χ2 test, Student’s t test, one-way analysis of variance, Kruskal–Wallis test, least significant difference test, and Pearson’s correlation coefficient for data analysis. Results Despite the significant difference of laboratory data between patient and control groups, least significant difference analysis revealed a nonsignificant difference between patients with T1DM and those with T2DM. On the level of the in-groups analysis, the most significant key players were hs-CRP and IL-6 among the three urinary albumin excretion rate categories of patients with T1DM and T2DM, with P values less than 0.01. Conclusions We concluded that IL-6 and hs-CRP might be used as sensitive markers for the development of DN. Keywords: C-reactive protein, diabetic nephropathy, interleukin 6