Introduction <p>Tissue reactions influence suture selection, particularly in the oral cavity. This study examined tissue reactions to nylon, vicryl, and silk sutures of various diameters in a rat model.</p> Materials and Methods <p>Thirty-six male Wistar rats (<i>n</i> = 12 per material) received 5-mm mucosal incisions bilaterally. Cheeks were closed with 3-0 (right) and 4-0 (left) suture threads. Each group was divided into two subgroups based on the 3rd and 7th day postoperatively. Stained samples were examined for histopathological evaluations in terms of fibrosis, granulation tissue formation, re-epithelialization, and inflammation. Data were analyzed using Fisher’s exact test (<i>p</i> &lt; 0.05).</p> Results <p>No significant differences were observed in inflammation grade, re-epithelialization, or granulation tissue formation between suture diameters (3-0 vs. 4-0) on postoperative days 3 or 7 (<i>p</i> &gt; 0.05). Across materials, a significant difference was detected only for fibrosis on day 3 among 4-0 sutures (<i>p</i> &lt; 0.01), with nylon showing the highest frequency. Within 4-0 silk, fibrosis was higher on day 7 than day 3 (<i>p</i> &lt; 0.05); no other day-related differences were significant.</p> Conclusion <p>Silk showed a non-significant tendency toward more severe inflammation, whereas vicryl showed a less pronounced tissue reaction. The within-animal comparison of 3-0 and 4-0 sutures showed broadly comparable histopathological outcomes, highlighting the value of evaluating suture diameter independent of material. A higher frequency of fibrosis was observed in silk and nylon groups. These exploratory findings may inform suture selection alongside cost and handling.</p>