Abstract. The aim of this investigation is to study the effect of donor concentration and microneedle (MN) length on permeation of insulin and further evaluating the data using scaling analyses and numerical simulations. Histological evaluation of skin sections was carried to evaluate the skin disruption and depth of penetration by MNs. Scaling analyses were done using dimensionless parameters like concentration of drug (C t /C s ), thickness (h/L) and surface area of the skin (S a /L 2 ). Simulation studies were carried out using MATLAB and COMSOL software to simulate the insulin permeation using histological sections of MN-treated skin and experimental parameters like passive diffusion coefficient. A 1.6-fold increase in transdermal flux and 1.9-fold decrease in lag time values were observed with 1.5 mm MN when compared with passive studies. Good correlation (R 2 >0.99) was observed between different parameters using scaling analyses. Also, the in vitro and simulated permeations profiles were found to be similar (f 2 ≥50). Insulin permeation significantly increased with increase in donor concentration and MN length (p<0.05). The developed scaling correlations and numerical simulations were found to be accurate and would help researchers to predict the permeation of insulin with new dimensions of MN in optimizing insulin delivery. Overall, it can be inferred that the application of MNs can significantly enhance insulin permeation and may be an efficient alternative for injectable insulin therapy in humans.