When molding macroscale polymer parts with a high density of microfeatures (>1 × 106/cm2), a concern that presents itself is the ability to achieve uniform replication across the entire domain. In the given study, micro-injection molding was used to manufacture microfeatured polymer substrates containing over 10 × 106 microfeatures per cm2. Polystyrene (PS) plates containing microtopography were molded using different processing parameters to study the effect of flow rate and mold temperature on replication quality and uniformity. Flow rate was found to significantly affect replication at mold temperatures above the glass transition temperature (Tg) of PS while having no significant effect on filling at mold temperatures below Tg. Moreover, replication was dependent on distance from the main cavity entrance, with increased flow rate facilitating higher replication differentials and higher replication near the gate. Simulation of the molding process was used to corroborate experimental trials. A deeper understanding of polymer fluid behavior associated with micro-injection molding is vital to reliably manufacture parts containing consistent microtopography (Note: Values are expressed in average ± standard error).