Introduction: Platelet-rich fibrin (PRF) has been widely applied for periodontal regeneration due to its simplicity, autologous nature and economics. This study aims to evaluate the variations in the fibrin network patterns of the PRF clot, which was isolated from chronic periodontitis patients with and without diabetes mellitus (DM). Materials and Methods: This study included 90 participants undergoing periodontal treatment therapy. The patients were divided into three groups: Group A (n = 30), chronic periodontitis patients without Type 2 DM; Group B (n = 30), chronic periodontitis patients with Type 2 DM (haemoglobin A1c [HbA1c], 6.5%–6.9%) and Group C (n = 30), chronic periodontitis patients with Type 2 DM (HbA1c ≥ 7%). The clinical parameters and blood samples were collected, and PRF preparation was done. Histological slide analysis was done in the stained section of the PRF clot and examined for the presence of dense and loose fibrin network patterns with the entrapments of platelets. Results: There was a significant difference in the dense and loose fibrin framework between chronic periodontitis patients without type 2 DM, chronic periodontitis patients with type 2 DM of 6.5–6.9 HbA1c and chronic periodontitis patients with type 2 DM of >7 HbA1c. Conclusion: Within the limitations of this study, future studies are needed to find the clinical outcomes of various PRF preparations in diabetic patients and other systemic factors that influence the fibrin network pattern, so that better regenerative outcomes can be achieved in patients with systemic diseases.