Introduction: The purpose of this study was to compare and Histological Effects of Propolis, Nigella sativa and Thymus vulgaris versus Formocresol for pulpotomy of vital primary molars.Materials and Methods: First part: extracts of Thymus vulgaris and Nigella sativa oil were prepared at laboratories of faculty of pharmacy and propolis extract was bought from Comvita ® Company.Second part: 80 primary molars indicated for vital pulpotomy from 20 children were selected from out clinics of Pediatric dentistry Department, Faculty of oral and dental medicine, Cairo University.Those teeth were divided into four equal groups according to materials used in this study. Propolis, Nigella sativa and Thymus vulgaris were mixed with zinc oxide powder only to make a paste and applied directly on pulp orifice after coronal pulp amputation (experimental groups).Formocresol was applied for 1 minute at least then zinc oxide eugenol paste was applied as usual treatment do (control group). All teeth restored with stainless steel crowns. Then, clinically with radiographically, during follow up period 1, 6 and 12 months after treatment.Third part: 48 teeth from 24 male albino rats were used for histological evaluation of materials used in study. Teeth were divided into four main groups according to the materials used then each group was divided into two sub groups according to the follow up period (14 days – 30days). Histological analysis was done after follow up.Results: By comparing investigated materials to the control group for pain presence during follow up results revealed (six teeth) with pain in (Nigella Sativa) group after 6 months with statistical significant difference p-value at ≤ 0.05. Tenderness also observed with one tooth after 6 month follow up in control group and Thymus vulgaris group after 12monts. One tooth showed abscess formation in control, Nigella Sativa and Thymus vulgaris groups in different follow up periods.Radiographic examination revealed furcation involvement or internal root resorption after treatment, which were evident in all groups in different times follow up with varying degrees.Highest number of teeth showed internal root resorption was within NS group after 12 months follow up with statically significance difference at p –value 0.009. However, decalcified sections of rat’s teeth after 14 and 30 days revealed that pulp tissue showed intact odontoblastic layer with different degrees of inflammation in connective tissue and small areas of hard tissue formation with different materials used.Conclusion: material investigated in this study showed promising results when the used as a substitute formocresol especially Propolis and Thymus vulgaris. However, nigella sativa oil expressed pain during follow up.