A reliable, inexpensive experimental counterpart of peripheral lymphedema has beennotoriously difficult to reproduce thereby stifling basic and clinical research into this frustratingclinical condition. Accordingly, in 45 adult Wistar-Fuzzy rats, we attempted to produce sustainedhindlimb lymphedema by either groin nodal/lymphatic microsurgical ablation (S)(guided byvisual blue dye lymphography) or limited field-groin irradiation (R) alone (4500 rads) orcombined S followed by R or R followed by S with an additional non-manipulated group servingas controls. Observations were made for 30-100 days thereafter. Hindlimb volumes weredetermined serially using the truncated cone formula based on multiple circumferentialmeasurements at standardized intervals along the affected hindlimb and the findings comparedwith similar measurements in the contralateral non-manipulated hindlimb. In randomly selectedrats from each group, lymphatic drainage was assessed by lymphangioscintigraphy (LAS), softtissue swelling by magnetic resonance imaging (MRI), and edema fluid total protein content byrefractometry. Whereas S or R alone produced only transient or mild hindlimb edema withoutassociated morbidity or mortality, SR or RS induced moderate to severe sustained protein-richhindlimb lymphedema associated with 9-13% early mortality and notable late local limbmorbidity. Lymphatic obstruction was documented by sustained maintenance of increasedhindlimb volume, subcutaneous fluid accumulation (MRI), and impaired lymphatic drainage (LAS). This reproducible rodent model of secondary lymphedema reliably simulates a stableclinical condition for a window of up to 100 days and should thereby facilitate standardizedtesting of therapeutic/preventive protocols and basic research into lymphatic dynamics insecondary lymphedema.