diff --git a/doc/source/whatsnew/v0.25.1.rst b/doc/source/whatsnew/v0.25.1.rst
index 69f82f7f85040..ae2ff33f3f219 100644
--- a/doc/source/whatsnew/v0.25.1.rst
+++ b/doc/source/whatsnew/v0.25.1.rst
@@ -56,7 +56,7 @@ Timezones
 
 Numeric
 ^^^^^^^
--
+- Bug in :meth:`Series.interpolate` when using a timezone aware :class:`DatetimeIndex` (:issue:`27548`)
 -
 -
 
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index 0afd42e406c1f..9053edf2d1424 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -30,7 +30,6 @@
     is_bool,
     is_bool_dtype,
     is_datetime64_any_dtype,
-    is_datetime64_dtype,
     is_datetime64tz_dtype,
     is_dict_like,
     is_extension_array_dtype,
@@ -7023,7 +7022,7 @@ def interpolate(
             methods = {"index", "values", "nearest", "time"}
             is_numeric_or_datetime = (
                 is_numeric_dtype(index)
-                or is_datetime64_dtype(index)
+                or is_datetime64_any_dtype(index)
                 or is_timedelta64_dtype(index)
             )
             if method not in methods and not is_numeric_or_datetime:
diff --git a/pandas/tests/series/test_missing.py b/pandas/tests/series/test_missing.py
index 8398591f1ff1f..8f4c89ee72ae1 100644
--- a/pandas/tests/series/test_missing.py
+++ b/pandas/tests/series/test_missing.py
@@ -1521,10 +1521,16 @@ def test_interp_nonmono_raise(self):
             s.interpolate(method="krogh")
 
     @td.skip_if_no_scipy
-    def test_interp_datetime64(self):
-        df = Series([1, np.nan, 3], index=date_range("1/1/2000", periods=3))
-        result = df.interpolate(method="nearest")
-        expected = Series([1.0, 1.0, 3.0], index=date_range("1/1/2000", periods=3))
+    @pytest.mark.parametrize("method", ["nearest", "pad"])
+    def test_interp_datetime64(self, method, tz_naive_fixture):
+        df = Series(
+            [1, np.nan, 3], index=date_range("1/1/2000", periods=3, tz=tz_naive_fixture)
+        )
+        result = df.interpolate(method=method)
+        expected = Series(
+            [1.0, 1.0, 3.0],
+            index=date_range("1/1/2000", periods=3, tz=tz_naive_fixture),
+        )
         assert_series_equal(result, expected)
 
     def test_interp_limit_no_nans(self):