The most common cause of lymphangitis in humans is bacteria, in which case sepsis and death could result within hours if left untreated.

In some cases, it can be caused by viruses such as mononucleosis or cytomegalovirus, as well as specific conditions such as tuberculosis or syphilis, and the fungus Sporothrix schenckii.

In very minor cases, regular application of antibiotic creams and cleanliness of the area can accelerate the healing process with no medical professional intervention or consultation required.

[9] When the inferior limbs are affected, the redness of the skin runs over the great saphenous vein location and can be confused for thrombophlebitis.

[10]: 261 To detect and identify infectious agents such as streptococci and staphylococci bacterial strains blood tests and bacteria cultures can be used.

[citation needed] Infectious lymphangitis should be differentiated from other conditions such as superficial thrombophlebitis (swelling is local to the affected vein), cat scratch (swellings feels hard to the touch), acute streptococcal hemolytic gangrene and necrotizing fasciitis (infected area crackles to the touch and the patient looks very ill).

Streptococci strains are the most common infectious agents and respond well to cephalosporins –  cephalexin at a dose of 0.5 mg for between 7 and 10 days – or extended-spectrum penicillin.

Methiciline-resistant staphylococcus aureus is common in communities and hence the need to use improved antibiotic drugs such as trimethoprim-sulfamethoxazole for 7 to 10 days.