Objectives: This study was conducted to compare between different implant number and distribution designed for assisting maxillary complete overdenture regarding the peri-implant IL-1β activity. Materials and Methods: Six completely edentulous patients were selected for this study. All patients received conventional complete dentures. After inserting the four implants for assisting the maxillary dentures and according to delayed loading protocol, the patients were divided randomly into three groups, Group A: 2 patients started the study with two exposed implants in the canine areas bilaterally to retain maxillary overdenture Group B:2 patients started the study with two exposed implants located in premolar areas bilaterally. Group C: 2 patients started the study with four exposed implants, located in the canine and premolar areas bilaterally. All implants were attached to the maxillary overdentures through OT equator attachments. Evaluation of peri-implant tissue was done 2 weeks, 3 months and 6 months after insertion of definitive overdenture. This was done by clinical evaluation of the peri implant tissues and by measuring the IL-1β values in the peri-implant sulcular fluid. Results: When comparing IL-1β values in PISF within each group in all intervals of study, there was a significant increase in values. When comparing between the three groups regarding the total means of IL-1β values around all implants along the T1 and T2 intervals, there was a significant difference. Conclusions: Within the limitation of this short term study, it is possible to conclude that: assisting the maxillary complete overdenture by four widely distributed implants retained by OT-Equator attachment can be considered more favorable than using only 2 implants either in the canine areas or in the premolar areas regarding the peri-implant IL-1β activity and the clinical evaluation.