Abstract: The objective of this research is to study the apoptosis of lymphocytes, sFas, and mRNA expression and serum level of TNF-α in children with Insulin dependent diabetes mellitus (IDDM) in order to explain an aspect of disease development and pancreatic β-cell death. The study included 71 children suffering from IDDM and 60 healthy children enrolled in the following groups; G1: included 28 children with recent onset of the disease, divided into: G1a included 8 with ketoacidosis, and G1b included 20 with nonketotic hyperglycemia; G2: included 43 undertreatment for more than 6 months, divided into: G2a included 7 with controlled status and G2b included 36 uncontrolled; G3: 60 normal children as control. For all the subjects the following have been done: detailed history, clinical examination and diagnostic investigations; detection of apoptotic cells by giemsa, acridine orange, propidium iodide and DNA fragmentation; measurements of sFas; mRNA of TNF-α; and serum levels of TNF-α The results showed that: sFas is decreased in patients with recent onset only. No significant difference between neither G1a and G1b nor between G2a and G2b. Low percentage of lymphocyte apoptotic cells detected by the three stains only in cases with recent onset; DNA fragmentation confirmed the apoptosis; mRNA and serum levels of TNF-α showed parallel results of increased levels in cases with recent onset. No significant difference neither between G1a vs G1b nor between G2a and G2b; positive correlation`s between sFas and apoptosis and between the results of apoptosis by the three stains; and negative correlation between sFas and apoptosis on one side and serum level of TNF-α on the other side. In conclusion, the inhibition of apoptosis result in accumulation and migration of immune reactive cells to infiltrate the islet cells of the pancreas. This together with the increased level of TNF-α may lead to the process of insulitis,and β-cells death by either apoptosis or necrosis.