Aim: The aim of the present study is to evaluate the effect of non surgical periodontal therapy on the level of interleukin-33 in the gingival crevicular fluid (GCF) of patients with chronic periodontitis before and after treatment and to compare it with healthy controls. Materials and Methods: The study included 15 patients suffering from chronic periodontitis and 10 healthy volunteers taken as a control group. Patients grouping: The first group consisted of 15 patients with moderate to advanced generalized chronic periodontitis, patient's age range from (35-55) years old. All patients who fulfilled the inclusion criteria were treated by non-surgical periodontal treatment (NSPT) which included scaling and root planning (SRP), and oral hygiene instructions (OHI). The second group consisted of 10 individuals with age ranging from (20 to 32) were selected from systemically and periodontally healthy. Preoperative examination: The periodontal measurements were performed using a Williams graduated periodontal probe. The clinical parameters were recorded as follows: plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment loss (CAL).Treatment plan: First group patients (Chronic periodontitis patients) received full mouth scaling and root planning (SRP) in two visits where two quadrants in each visit, using ultrasonic scalers and hand instruments. Patients were given careful instructions on self performed plaque control measures. Collection of gingival cervical fluid (GCF) sample:All clinical parameters were recorded the day before sample collection. Areas to be sampled were selected from the deepest periodontal pocket in every individual. GCF samples were collected at the initial visit for both groups and in chronic periodontitis patients 6 weeks after NSPT.Enzyme linked immuno-sorbent assay (ELISA): GCF samples of patients were assayed using ELISA technique for estimation of the level of interleukins 33 in GCF. Commercial interleukin-33 by ELISA kit was used to analyze IL-33 level in GCF. The kit employed a quantitive "sandwich" enzyme immunoassay technique. Results: There was insignificant negative relationship between IL-33 (pg/ml) and Age. There was insignificant positive relationship between IL-33 (pg/ml) and Gender. There was insignificant negative relationship between IL-33 (pg/ml) and PI. There was insignificant negative relationship between IL-33 (pg/ml) and GI. There was significant relationship between IL-33 (pg/ml) and PPD. There was insignificant negative relationship between IL-33 (pg/ml) and CAL. Conclusions were derived: •Non surgical periodontal treatment resulted in significant improvement in all clinical parameters in chronic periodontitis group with significant increase in the level of IL-33 in GCF after treatment when compared to before treatment.•The mean GCF level of IL-33 was insignificant between healthy controls and chronic periodontitis patients after treatment.•These data suggest that IL-33 amount in GCF reflects limited role of this biomarker in the initiation of periodontal inflammation.Clinical recommendations: Further studies are needed to detect the action of IL-33 by evaluating gene expression of this cytokine from gingival tissue biopsies.