Prior to sealing off any points of entry, confirm that no animals are living in your duct work so you do not inadvertently trap them inside. Typically, there are rather obvious signs if an animal has made your ventilation system its new home: You will hear it scampering and scratching about. Because animals often come and go, search for traces of them as well, such as droppings and damage. Use a flashlight to search for these signs in the air vents and in the areas of your home where the duct work is located, typically in the attic or basement. Because your search will be limited to just the ends of the vents where you have access, consult a professional to inspect further to ensure there are no animals present. Should you discover an animal is residing in your duct work, have a professional remove it.
Once you have determined that there are no animals inside your duct work, inspect the exterior of your home for possible points of entry. These are often the vents on the outside of your house. Place wire mesh over any open vents to prevent rodent entry. This is a very durable material, will not rust, and can be shaped. You can buy it in rolls at almost any hardware store. Take care not to impede the ventilation with vent coverings. You should consult a professional or someone at the hardware store for suggestions on wire mesh gauges that are appropriate for vent coverings. Typically 1/2 inch by 1/2 inch is the gauge used to keep small animals from entering.
Seal up any other points of entry in the exterior of your home such as holes and cracks in the structure. The animals may not have entered through the ventilation system, but they are not barred from entering the ventilation system once inside. You can fill cracks in siding, eaves, and seams with painter's caulking, which can be painted the appropriate color once it dries. For holes, you will need to apply a filler prior to caulking. Wire mesh and steel wool are best for this because they are more durable, cleaner, and less expensive than expanding foam fillers.