Background: Given the serious health consequences including impaired metabolic control among type 1 diabetes mellitus (T1DM), neuropeptide B (NPB), neuropeptide W (NPW), leptin and adiponectin collectively could serve as biomarkers of T1DM progression. Objectives: Comparison of serum levels of NPB, NPW, leptin and adiponectin among children and adolescents with T1DM treated either by multiple daily doses of insulin (MDI) or continuous subcutaneous insulin infusion (CSII), and healthy age and sex matched controls. Patients and methods: This comparative cross-sectional study included 60 children and adolescents with type 1 diabetes mellitus divided equally into 2 groups according to the type of insulin regimen (MDI or CSII). The cases were recruited from attendees of the Pediatrics and Adolescents Diabetes Unit (PADU), Children's Hospital, Ain Shams University, Cairo, Egypt. Cases were compared to 30 healthy age and sex-matched controls. Demographic and anthropometric data, medical history, estimated glucose disposal ratio and glycated hemoglobin were collected. Measurements of NPB, NPW, leptin and adiponectin were performed using enzyme-linked immunosorbent assay (ELISA). Results: There was a significant difference between the diabetic groups and the control group regarding NPB, NPW, leptin and adiponectin, where NPB, NPW and leptin levels were significantly decreased among MDI and CSII groups compared to the control group (p=0.001), while adiponectin was significantly increased among the MDI and CSII groups compared to the control group (p=0.001). However, there was no statistically significant difference between the MDI and CSII groups (p>0.05). Conclusion: The lower levels of NPB, NPW and leptin among both MDI and CSII groups could be attributed to decreased body fat, and lower BMI which is a reflection of their metabolic control. Similarly, elevation in adiponectin among both MDI and CSII groups compared to the control group might be a result of hyperglycemia and impaired glycosylation process. Further studies on larger scale are warranted to confirm our data.